Project Summary DNA sequencing is increasingly being used in clinical research in genetic disease and oncology. Currently most clinical sequencing is carried out using short-read targeted sequencing methods to detect mutations in protein-coding regions of the genome. However, short-read sequencing methods are not well suited to detection of alterations involving DNA segments greater than 100 base pairs in length, nor can they detect the arrangement of sequence polymorphisms that are more than a few hundred bases apart on a chromosome. Such long-range genomic analyses are becoming increasingly important, and new long-read sequencing technologies have been developed that can address these technical problems. However, the new long-read sequencing methods are roughly 10-fold more expensive than commonly-used short-read sequencing methods. Our proposal seeks to develop an instrument system that can isolate specific long genomic DNA fragments (100,000 to 1 million base pairs in length) from biological samples, and thereby provide a new economical approach for targeted long-read sequencing sample preparation. The proposed system is intended for robust, high sample throughput, walk-away automated processing in high volume genome centers and clinical laboratories.